Lwere Kamada, Muwonge Haruna, Sendagire Hakim, Sajatovic Martha, Gumukiriza-Onoria Joy Louise, Buwembo Denis, Buwembo William, Nassanga Rita, Nakimbugwe Rheem, Nazziwa Aisha, Munabi Ian Guyton, Nakasujja Noeline, Kaddumukasa Mark
Department of Microbiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
Department of Microbiology, Faculty of Health Sciences, Soroti University, Soroti, Uganda.
Medicine (Baltimore). 2025 May 9;104(19):e42407. doi: 10.1097/MD.0000000000042407.
Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by cognitive decline and progressive functional impairment. The Apolipoprotein E (APOE) gene, particularly its ε2, ε3, and ε4 alleles, plays a crucial role in lipid metabolism, and has been implicated in AD pathogenesis. Although the APOE ε4 status is associated with an increased risk of AD, its impact varies across populations. This study investigated the prevalence of and association between APOE alleles and AD risk in a Ugandan cohort. This case-control study was conducted in Uganda, and included 87 participants (45 patients with AD and 42 healthy controls). Cognitive assessment was performed using the Montreal Cognitive Assessment (MoCA) and clinical diagnoses were based on the ICD-11 and DSM-5 criteria. Venous blood was collected for APOE genotyping by polymerase chain reaction. Statistical analyses, including logistic regression and generalized additive models (GAMs), were used to assess the association between APOE alleles and AD risk after adjusting for age, education, and sex. This study included 45 patients with AD and 42 healthy controls. The AD group was significantly older than controls (79.6 vs 73.0 years; P = .0006). The ε4 allele was common in both the AD (42.2%) and control groups (44.0%), which was higher than the 1000 Genomes African ancestry data. No significant association was found between the APOE genotype or allele dosage and AD risk after adjusting for age, sex, and education. However, the probability of AD increases with age, particularly among ε4 carriers with lower educational levels. While APOE ε4 status was associated with a higher predicted probability of AD in older adults, no statistically significant relationship was observed in the Ugandan cohort. These findings support the need for larger population-specific studies to explore APOE's role of APOE in AD risk across sub-Saharan Africa.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征为认知能力下降和进行性功能损害。载脂蛋白E（APOE）基因，尤其是其ε2、ε3和ε4等位基因，在脂质代谢中起关键作用，并与AD发病机制有关。尽管APOE ε4状态与AD风险增加相关，但其影响在不同人群中有所不同。本研究调查了乌干达队列中APOE等位基因的流行情况及其与AD风险的关联。这项病例对照研究在乌干达进行，纳入了87名参与者（45例AD患者和42名健康对照）。使用蒙特利尔认知评估量表（MoCA）进行认知评估，临床诊断基于国际疾病分类第11版（ICD - 11）和精神疾病诊断与统计手册第5版（DSM - 5）标准。采集静脉血通过聚合酶链反应进行APOE基因分型。统计分析，包括逻辑回归和广义相加模型（GAMs），用于在调整年龄、教育程度和性别后评估APOE等位基因与AD风险之间的关联。本研究包括45例AD患者和42名健康对照。AD组患者的年龄显著大于对照组（79.6岁对73.0岁；P = 0.0006）。ε4等位基因在AD组（42.2%）和对照组（44.0%）中都很常见，高于千人基因组计划中的非洲血统数据。在调整年龄、性别和教育程度后，未发现APOE基因型或等位基因剂量与AD风险之间存在显著关联。然而，AD的患病概率随年龄增加，特别是在教育水平较低的ε4携带者中。虽然APOE ε4状态与老年人中AD的较高预测概率相关，但在乌干达队列中未观察到统计学上的显著关系。这些发现支持需要开展更大规模的针对特定人群的研究，以探索APOE在撒哈拉以南非洲地区AD风险中的作用。
